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| Status |
Public on Mar 26, 2020 |
| Title |
Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors, and characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with obesity and T2D, of which the majority is located in non-coding DNA regions. This suggest that most variants mediate their effect by altering the activity of gene-regulatory elements, including enhancers. Here, we map skeletal muscle genomic enhancer elements that are dynamically regulated after exposure to the free fatty acid palmitate or the inflammatory cytokine TNFα. By overlapping enhancer positions with the location of disease-associated genetic variants, and resolving long-range chromatin interactions between enhancers and gene promoters, we identify target genes involved in metabolic dysfunction in skeletal muscle. The majority of these genes also associate with altered whole-body metabolic phenotypes in the murine BXD genetic reference population. Thus, our combined genomic investigations identified genes that are involved in skeletal muscle metabolism and linked to SNPs associated with the development of obesity and T2D.
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| Overall design |
H3K27ac & H3K4me1 ChIP of human primary muscle cells treated with palmitate or TNFa.
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| Web link |
https://github.com/lars-work-sund/Skeletal-muscle-enhancer-interactions-identify-genes-controlling-human-metabolism
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| |
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| Contributor(s) |
Williams K, Ingerslev LR, Bork-Jensen J, Wohlwend M, Hansen AN, Small L, Ribel-Madsen R, Astrup A, Pedersen O, Auwerx J, Workman CT, Grarup N, Hansen T, Barrès R |
| Citation(s) |
32483258 |
| Submission date |
Feb 05, 2019 |
| Last update date |
Jun 22, 2020 |
| Contact name |
Lars Roed Ingerslev |
| E-mail(s) |
ingerslev@sund.ku.dk
|
| Organization name |
Copenhagen University
|
| Department |
NNF Center for Basic Metabolic Research
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| Lab |
Integrative Physiology
|
| Street address |
Blegdamsvej 3B
|
| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (25)
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| This SubSeries is part of SuperSeries: |
| GSE126102 |
Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans |
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| Relations |
| BioProject |
PRJNA521022 |
| SRA |
SRP183729 |
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